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master's thesis
Primjena niskotemperaturnih eutektičkih otapala za razvoj formulacije lijekova s klotrimazolom kao aktivnim farmaceutskim sastojkom
Zagreb: University of Zagreb, Faculty of Food Technology and Biotechnology, 2021. urn:nbn:hr:159:116011
Sopić, Tihana
University of Zagreb
Faculty of Food Technology and Biotechnology
Department of Biochemical Engineering
Laboratory for Cell Technology, Application and Biotransformations

Institutional repository: Repository of the Faculty of Food Technology and Biotechnology

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Sopić, T. (2021). Primjena niskotemperaturnih eutektičkih otapala za razvoj formulacije lijekova s klotrimazolom kao aktivnim farmaceutskim sastojkom (Master's thesis). Zagreb: University of Zagreb, Faculty of Food Technology and Biotechnology. Retrieved from https://urn.nsk.hr/urn:nbn:hr:159:116011

Sopić, Tihana. "Primjena niskotemperaturnih eutektičkih otapala za razvoj formulacije lijekova s klotrimazolom kao aktivnim farmaceutskim sastojkom." Master's thesis, University of Zagreb, Faculty of Food Technology and Biotechnology, 2021. https://urn.nsk.hr/urn:nbn:hr:159:116011

Sopić, Tihana. "Primjena niskotemperaturnih eutektičkih otapala za razvoj formulacije lijekova s klotrimazolom kao aktivnim farmaceutskim sastojkom." Master's thesis, University of Zagreb, Faculty of Food Technology and Biotechnology, 2021. https://urn.nsk.hr/urn:nbn:hr:159:116011

Sopić, T. (2021). 'Primjena niskotemperaturnih eutektičkih otapala za razvoj formulacije lijekova s klotrimazolom kao aktivnim farmaceutskim sastojkom', Master's thesis, University of Zagreb, Faculty of Food Technology and Biotechnology, accessed 26 November 2024, https://urn.nsk.hr/urn:nbn:hr:159:116011

Sopić T. Primjena niskotemperaturnih eutektičkih otapala za razvoj formulacije lijekova s klotrimazolom kao aktivnim farmaceutskim sastojkom [Master's thesis]. Zagreb: University of Zagreb, Faculty of Food Technology and Biotechnology; 2021 [cited 2024 November 26] Available at: https://urn.nsk.hr/urn:nbn:hr:159:116011

T. Sopić, "Primjena niskotemperaturnih eutektičkih otapala za razvoj formulacije lijekova s klotrimazolom kao aktivnim farmaceutskim sastojkom", Master's thesis, University of Zagreb, Faculty of Food Technology and Biotechnology, Zagreb, 2021. Available at: https://urn.nsk.hr/urn:nbn:hr:159:116011

Metadata
TitlePrimjena niskotemperaturnih eutektičkih otapala za razvoj formulacije lijekova s klotrimazolom kao aktivnim farmaceutskim sastojkom
Title (english)Application of deep eutectic solvent for development of drug formulation with clotrimazole as an active pharmaceutical ingredient
AuthorTihana Sopić
MentorKristina Radošević (mentor)
Committee memberIvana Radojčić Redovniković (član povjerenstva)
GranterUniversity of Zagreb
Faculty of Food Technology and Biotechnology
(Department of Biochemical Engineering)
(Laboratory for Cell Technology, Application and Biotransformations)
Zagreb
Defense date and country2021-09-29, Croatia
Scientific / art field,
discipline and subdiscipline		BIOTECHNICAL SCIENCES
Biotechnology
Abstract
Niskotemperaturna eutektička otapala (DES) intenzivno se istražuju kao zelena otapala za razvoj novih formulacija lijekova, prvenstveno za poboljšanje topljivosti, stabilnosti i permeabilnosti aktivnog farmaceutskog sastojka (API). U ovom radu, topljivost klotrimazola u različitim DES-ovima predviđena je korištenjem računalnog programa COSMOtherm, pri čemu je najbolja topljivost predviđena u hidrofobnim otapalima. Za eksperimentalno određivanje topljivosti pripremljena su tri DES-a, a najbolja topljivost iznosila je 151,62 mg mL-1 u otapalu timol:oktanska kiselina molarnog omjera 1:3, što je određeno tekućinskom kromatografijom visoke djelotvornosti. Stabilnost formulacije praćena je spektrofotometrijski tijekom vremena, na sobnoj temperaturi i +4 °C. Klotrimazol se nije pokazao stabilnim, čak ni uz dodatak β-ciklodekstrina. Citotoksičnost formulacije i DES-a ispitana je na HaCaT staničnoj liniji u rasponu koncentracija 0,01-10 mg mL-1, pri čemu nije uočen značajan negativan učinak na rast stanica. Testom propusnosti umjetne membrane (PAMPA) određeno je da u formulaciji s DES-om nije postignuto poboljšanje permeabilnost API-ja. Iako razvijena formulacija klotrimazola u timol:oktanska kiselina pokazuje značajno bolju topljivost API-ja obzirom na referentno otapalo i nisku citotoksičnost tako pripravljene formulacije, potrebna su daljnja ispitivanja s drugim DES-ovima kako bi se riješilo pitanje stabilnosti API-ja u takvoj formulaciji i postigla bolja permeabilnosti.
Abstract (english)
Deep eutectic solvents (DES) are being intensively investigated as green solvents for the development of new drug formulations, primarily to improve the solubility, stability and permeability of the active pharmaceutical ingredient (API). In this work, the solubility of clotrimazole in different DESs was predicted using the computer program COSMOtherm, with the best solubility predicted in hydrophobic solvents. Three DESs were prepared for the experimental determination of solubility, and the best solubility was 151,62 mg mL-1 in solvent thymol: octanoic acid with a molar ratio of 1:3, as determined by high performance liquid chromatography. The stability of the formulation was monitored spectrophotometrically over the time, at room temperature and +4 °C. Clotrimazole was not stable, even with the addition of β-cyclodextrin. The cytotoxicity of the formulation and DES was examined on the HaCaT cell line in the concentration range 0,01-10 mg mL-1, but no significant negative effect on cell growth was observed. The parallel artificial membrane permeability assay (PAMPA) showed that DES formulation did not improve API permeability. Although in the developed formulation of clotrimazole in thymol: octanoic acid significant improvment in solubility was achived and low cytotoxicity was observed, further research with other DESs is needed to solve the stability of the API in such formulation and to achieve better permeability.
Keywords
Keywords (english)
Languagecroatian
URN:NBNurn:nbn:hr:159:116011
Study programmeTitle: Molecular Biotechnology
Study programme type: university
Study level: graduate
Academic / professional title: magistar/magistra inženjer/inženjerka molekularne biotehnologije (magistar/magistra inženjer/inženjerka molekularne biotehnologije)
Type of resourceText
File originBorn digital
Access conditionsOpen access
Terms of useLicence Attribution-NoDerivatives 4.0 International (CC BY-ND 4.0) icon
Created on2021-10-25 10:42:56